| SUN Jian,LIU Ning-bo,ZHUANG Hong-qing,ZHAO Lu-jun,YUAN Zhi-yong,WANG Ping.Enhancement of radiation sensitivity by erlotinib and celecoxib in A549 human lung cancer cell line[J].Chinese Journal of Radiological Medicine and Protection,2012,32(2):186-190 |
| Enhancement of radiation sensitivity by erlotinib and celecoxib in A549 human lung cancer cell line |
| Received:May 19, 2010 |
| DOI：10.3760/cma.j.issn.0254-5098.2012.02.020 |
| KeyWords:Celecoxib|Erlotinib|Lung adenocarcinoma|Radiosensitization |
| FundProject: |
| Author Name | Affiliation | | SUN Jian | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China | | LIU Ning-bo | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China | | ZHUANG Hong-qing | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China | | ZHAO Lu-jun | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China | | YUAN Zhi-yong | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China | | WANG Ping | Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tainjin 300060, China |
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| Abstract:: |
| Objective To investigate the role of epidermal growth factor receptor and cyclooxygenase-2 pathways in the erlotinib and celecoxib enhanced radiation sensitivity in A549 human lung cancer cell line. Methods IC20 of erlotinib and celecoxibon in A549 human lung cancer cells was measured by MTT assay. Clonogenic assays were used to evaluate the antitumor effects of the drugs and X-irradiation. Flow cytometry was used to assess the apoptosis and cell cycle alteration, and Western blot was used for the detection of Akt and phospho-Akt. Results Both erlotinib and celecoxib could inhibit the proliferation of A549 cells in vitro in a dose-dependent manner and their values of IC20 were (5.15±0.14) and (40.32±1.26) μmol/L, respectively. For radiation survival, the values of Dq,D0,SF2 of the combination of two drugs were lower than those of either drug (t=6.62, P<0.05).The SER of celecoxib, erlotinib and their combination were 1.299, 1.503 and 2.217, respectively. Flow cytometry assay showed that both celecoxib and erlotinib could enhance radiation-induced G0 /G1 arrest, reduce the cell numbmer in S phase,and enhance radiation-induced apoptosis, especially for the combination of drugs. Western blot assay showed that the expressions of Akt protein were similar in all groups. However, pAkt expression was suppresssed by erlotinib and celecoxib, but promoted by radiation. pAkt had the lowest expression in the radiated cells with the treatment of two drugs (t=4.89, P<0.05). Conclusions The erlotinib and/or celecoxib could enhance radiosensitivity probably by increasing cell apoptosis and reducing the number of S-phase cells with low radiosensitivity. |
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